A viral gene that activates lytic cycle expression of Kaposi’s sarcoma-associated herpesvirus

TLDR

Herpesviruses alternate between latency and a lytic productive cycle, and the immediate‑early gene studied here is homologous to Epstein–Barr virus Rta. The study identifies a KSHV‑encoded immediate‑early gene that activates lytic cycle gene expression from the latent viral genome. KSHV/Rta induces early lytic genes such as IL‑6 and PAN RNA and the late capsid antigen, activates only its own lytic genes in dual EBV/KSHV infections, and its cytokine‑driving activity may contribute to KSHV‑associated disease pathogenesis.

Abstract

Herpesviruses exist in two states, latency and a lytic productive cycle. Here we identify an immediate-early gene encoded by Kaposi’s sarcoma-associated herpesvirus (KSHV)/human herpesvirus eight (HHV8) that activates lytic cycle gene expression from the latent viral genome. The gene is a homologue of Rta, a transcriptional activator encoded by Epstein–Barr virus (EBV). KSHV/Rta activated KSHV early lytic genes, including virus-encoded interleukin 6 and polyadenylated nuclear RNA, and a late gene, small viral capsid antigen. In cells dully infected with Epstein–Barr virus and KSHV, each Rta activated only autologous lytic cycle genes. Expression of viral cytokines under control of the KSHV/Rta gene is likely to contribute to the pathogenesis of KSHV-associated diseases.